It has been known for some time that gastrin, histamine, and acetylcholine regulate gastric acid secretion, but the precise nature of the interaction of stimuli as well as their action on the parietal cell is still unknown. The purpose of the present investigation is to delineate the biochemical events which occur in the parietal cell in response to these hormones. In particular, attempts will be made to evaluate not only the individual role of calcium in mediating secretagogue stimulation, but will also consider the possible interactions of calcium, cyclic AMP and cyclic GMP. A concerted approach to this problem will include a determination of whether the gastric secretagogues directly alter the calcium transport properties of isolated parietal cells and whether any changes in intracellular calcium concentration are correlated with alterations in cyclic nucleotide levels and parietal cell function. At the biochemical level, we will attempt to delineate the mechanisms by which the enzymes involved in cyclic nucleotide metabolism and calcium transport are regulated and to establish whether the calcium-dependent regulatory protein, calmodulin, mediates the possible effects of calcium in regulating gastric secretion. Since phosphorylation of the plasma membrane may be the final event of hormone-induced acid secretion, the proposed studies will attempt to define the specific role of protein kinases in regulating morphological and functional changes in the parietal cell plasmalemma. By correlating changes in intracellular second messenger levels and phosphorylation state of the membrane with changes in transport properties of isolated parietal cells, the elucidation of the mechanism by which hydrogen-secretion is modulated may be attainable.